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DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily

High local control in early stage (I/II) non-small-cell lung cancer

DART-bid: dosisdifferenzierte akzelerierte Radiotherapie, 2 × 1,8 Gy täglich

Hohe lokale Kontrolle bei nichtkleinzelligem Bronchialkarzinom im Frühstadium (I/II)

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Abstract

Background

While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid).

Patients and methods

Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for <  2.5 cm, 79.2 Gy for 2.5–4.5 cm, 84.6 Gy for 4.5–6 cm, 90 Gy for > 6 cm.

Results

The median follow-up was 28.5 months (range 2–108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤  grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis.

Conclusion

DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts.

Zusammenfassung

Hintergrund

Die Standardbehandlung für nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie für Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative akzeptiert ist. Internationale Leitlinien empfehlen verschiedene Therapieoptionen, darunter Körperstereotaxie für kleine Tumoren, konventionelle Radiotherapie ≥ 60 Gy für größere insbesondere zentral gelegene Tumoren oder eine Behandlung nach dem CHART("continuous hyperfractionated accelerated radiotherapy")-Regime. Diese Studie zeigt klinische Ergebnisse und Toxizität nach akzelerierter Radiotherapie mit 2 × 1,8 Gy täglich (DART-bid).

Patienten und Methoden

Von 04/2002 bis 12/2010 wurden 54 Patienten (medianes Alter 71 Jahre, medianer Karnofsky-Index 70 %) mit NSCLC im Frühstadium behandelt. Die Gesamtdosis wurde nach Tumordurchmesser verordnet: 73,8 Gy (< 2,5 cm), 79,2 Gy (2,5–4 cm), 84,6 Gy (4,5–6 cm), 90 Gy (> 6 cm).

Ergebnisse

Die mediane Nachsorgedauer aller Patienten betrug 28,5 Monate (2–108), die aktuarische Lokalkontrolle (LC) nach 2 und 3 Jahren 88 % und die regionäre Kontrolle 100 %. Tumorbedingt verstarben 10/54 (19 %) Patienten, 18/54 (33 %) an kardiovaskulären oder pulmonalen Erkrankungen. Interkurrent verstarben 11/54 (20 %) Patienten, wobei die Tumorerkrankung zum Zeitpunkt der letzten Nachsorge kontrolliert war und keine therapieassoziierte Toxizität feststellbar war; 15/54 (28 %) Patienten leben noch. Sieben Patienten erlitten eine akute Ösophagitis ≤ Grad 2, 2 eine chronische Lungenfibrose Grad 2.

Schlussfolgerung

DART-bid ermöglicht eine hohe Lokalkontrollrate ohne wesentliche Toxizität. Insbesondere für zentral gelegene und/oder große (> 5 cm) Tumoren, bei denen eine Körperstereotaxie nicht durchführbar ist, könnte diese Methode als mögliche radiotherapeutische Alternative zu den derzeit gültigen Empfehlungen dienen, mit der Notwendigkeit der Validierung in größeren Kohorten.

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Compliance with ethical guidelines

Conflict of interest

F. Zehentmayr, K. Wurstbauer, H. Deutschmann, C. Fussl, P. Kopp, K. Dagn, G. Fastner, P. Porsch, M. Studnicka, and F. Sedlmayer state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients.

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Authors and Affiliations

  1. Univ.-Klinik für Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversität, Landeskrankenhaus Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria

    Franz Zehentmayr M.D., M.Sc., Karl Wurstbauer M.D., Heinz Deutschmann M.Sc., Christoph Fussl M.D., Peter Kopp Ph.D., Karin Dagn M.D., Gerd Fastner M.D. & Felix Sedlmayer M.D.

  2. Institute for Research and Development of Advanced Radiation Technologies (radART), Paracelsus Medizinische Privatuniversität, Salzburg, Austria

    Franz Zehentmayr M.D., M.Sc., Karl Wurstbauer M.D., Heinz Deutschmann M.Sc. & Felix Sedlmayer M.D.

  3. Univ.-Klinik für Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversität, Landeskrankenhaus Salzburg, Salzburg, Austria

    Peter Porsch M.D. & Michael Studnicka M.D.

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  1. Franz Zehentmayr M.D., M.Sc.
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Correspondence to Franz Zehentmayr M.D., M.Sc..

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Zehentmayr, F., Wurstbauer, K., Deutschmann, H. et al. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. Strahlenther Onkol 191, 256–263 (2015). https://doi.org/10.1007/s00066-014-0754-6

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  • DOI: https://doi.org/10.1007/s00066-014-0754-6

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